Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Induction of hormesis and adaptive response by low-dose radiation (LDR) has been extensively indicated. Adaptive response induced by LDR was not only resistant to damage caused by a subsequently high-dose radiation, but also cross-resistant to other non-radiation challenges, such as chemicals. Mechanisms by which LDR induces the preventive effect on radiation- or chemical-induced tissue damage include induced or up-regulated expression of protective proteins, such as heat shock proteins and antioxidants. Since oxidative damage to tissues is a major pathogenesis of many human diseases including diabetes, this review will summarize the available data with an emphasis of the preventive effect of LDR on the development of diabetes and the therapeutic effect of LDR on diabetic cardiovascular complications. The available data indicated that pre-exposure of mice to LDR reduced the incidence of alloxan-induced diabetes, and also delayed the onset of hyperglycaemia in diabetes-prone non-obese diabetic mice. Experiments with animals indicated the effectively therapeutic effect of low-intensity or power laser (LIL or LPL) radiation on skin wound healing, which has stimulated clinical use of LIL to cure skin ulcer in diabetic patients. Mechanisms by which LDR prevents diabetes, though are unclear now, may include the induction of pancreatic antioxidants to prevent beta cell from oxidative damage and immunomodulation to preserve pancreatic function. For LIL therapeutic effect on diabetic wound healing, mechanisms may include its antioxidant action, immunomodulation, cell proliferation stimulation as well as improvement of systemic and wound-regional microcirculation. Therefore, although only a few studies indicating LDR prevention of the development of diabetes, many studies have demonstrated LDR, specifically LIL, therapeutic effectiveness of diabetic wound healing. These preliminary results are really encouraging for us to further pursue the clinical implication of LDT to diabetes-related areas.
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PMID:Low-dose radiation and its clinical implications: diabetes. 1848 Jan 38

A number of human and animal studies using conjugated linoleic acids (CLA) or diacylglycerol (DAG) oil have shown positive physiological effects on abdominal adiposity, plasma triglycerides, plasma glucose, and insulin sensitivity. A novel DAG composition containing CLA called CLA diacylglyceride (CLA-DAG) may offer potential as a therapeutic agent in reducing some of the symptoms associated with the diabetic phenotype and metabolic syndrome. This study was designed to investigate the effect of CLA-DAG oil on the diabetic phenotype in male Zucker diabetic fatty rats. Animals were assigned to one of four groups: control (C), rosiglitazone (ROS), CLA-DAG, or CLA as free fatty acid (CLA-FFA). After 11 weeks, body weight was higher and kidney weight was lower in the CLA-DAG and ROS groups compared with the C group. The ROS treatment increased the percentage of body fat as compared with all other groups. Final fasting blood glucose was lower in the CLA-DAG and ROS groups than in the C group. Plasma cholesterol was lower in the CLA-DAG group, and plasma triglycerides were lower in the ROS group compared with the C group. We also observed changes in transcript abundance of PPAR-gamma, PPAR-alpha, FAS, LPL, UCP2, UCP3, CPT1, RxR, ObRb, ApoAII, ApoD, and IRS1 in liver, muscle, and adipose tissue, suggesting treatment-induced effects on these genes. Collectively, these data suggest the need for further research on the therapeutic relevance of CLA-DAG oil in obesity and diabetes. Future research should also differentiate between CLA alone and DAG alone compared with the combination.
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PMID:A combination of CLA-DAG oil modifies the diabetic phenotype in male Zucker diabetic fatty rats. 1854 85

Recent genome-wide association (GWA) studies have identified new genetic determinants of complex quantitative traits, including plasma triglyceride (TG). We hypothesized that common variants associated with mild TG variation identified in GWA studies would also be associated with severe hypertriglyceridemia (HTG). We studied 132 patients of European ancestry with severe HTG (fasting plasma TG > 10 mmol/l), who had no mutations found by resequencing of candidate genes, and 351 matched normolipidemic controls. We determined genotypes for: GALNT2 rs4846914, TBL2/MLXIPL rs17145738, TRIB1 rs17321515, ANGPTL3 rs12130333, GCKR rs780094, APOA5 rs3135506 (S19W), APOA5 rs662799 (-1131T > C), APOE (isoforms) and LPL rs328 (S447X). We found that: (i) genotypes, including those of APOA5 S19W, APOA5 -1131T > C, APOE, GCKR, TRIB1 and TBL2/MLXIPL, were significantly associated with severe HTG; (ii) odds ratios for these genetic variables were significant in both univariate and multivariate regression analyses, irrespective of the presence or absence of diabetes or obesity; (iii) a significant fraction-about one-quarter-of the explained variation in disease status was associated with these genotypes. Therefore, common SNPs (single nucleotide polymorphisms) that are associated with mild TG variation in GWA studies of normolipidemic subjects are also associated with severe HTG. Our findings are consistent with the emerging model of a complex genetic trait. At the extremes of a quantitative trait, such as severe HTG, are found the cumulative contributions of both multiple rare alleles with large genetic effects and common alleles with small effects.
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PMID:Polygenic determinants of severe hypertriglyceridemia. 1859 51

Type 2 diabetes is a situation at high cardiovascular risk, characterized by platelet hyperactivation, oxidative stress, elevated very-low density lipoprotein (VLDL) and low high-density lipoprotein concentrations. In the present report, we describe the effects of these alterations on the transfers of phospholipids (PL) from VLDL to platelets in basal conditions or after thrombin (0.1U/mL) or lipoprotein lipase (LPL, 500ng/mL)-mediated platelet activation. In vitro transfer of radiolabelled PL from VLDL (200microM PL) to platelets (2x10(8)/mL) was measured after incubations of 1h at 37 degrees C in a series of recombination experiments using control or diabetic platelets and VLDL, as well as normal or oxidized PL. Basal- and thrombin-stimulated transfers from diabetic VLDL were similar to those from control VLDL. However, LPL-stimulated transfer was decreased when using diabetic VLDL. This was likely due to their lowered ability to be lipolyzed. When we compared the platelets from either diabetic patients or control subjects, we observed that the transfers of PL from control VLDL to diabetic platelets were 20-30% higher than those to control platelets, whether in basal conditions or under LPL or thrombin stimulations. Finally, we observed that, in all conditions tested, the rate of transfers of oxidized PL was two to three times more elevated than that of non oxidized PL. Collective consideration of these data suggests that the transfer of PL from VLDL to platelets might be elevated in type 2 diabetes, favoring oxidative stress-mediated platelet hyperactivation.
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PMID:Alterations in the transfer of phospholipids from very-low density lipoproteins to activated platelets in type 2 diabetes. 1861 95

Myocardial infarction (MI) is an important clinical problem because of its large contribution to mortality. The main causal and treatable risk factors for MI include hypertension, hypercholesterolemia or dyslipidemia, diabetes mellitus, and smoking. In addition to these risk factors, recent studies have shown the importance of genetic factors and interactions between multiple genes and environmental factors. Disease prevention is an important strategy for reducing the overall burden of MI, with the identification of markers for disease risk being key both for risk prediction and for potential intervention to lower the chance of future events. Although genetic linkage analyses of families and sib-pairs as well as candidate gene and genome-wide association studies have implicated several loci and candidate genes in predisposition to coronary heart disease (CHD) or MI, the genes that contribute to genetic susceptibility to these conditions remain to be identified definitively. In this review, we summarize both candidate loci for CHD or MI identified by linkage analyses and candidate genes examined by association studies. We also review in more detail studies that have revealed the association with MI or CHD of polymorphisms in MTHFR, LPL, and APOE by the candidate gene approach and those in LTA and at chromosomal region 9p21.3 by genome-wide scans. Such studies may provide insight into the function of implicated genes as well as into the role of genetic factors in the development of CHD and MI.
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PMID:Molecular genetics of myocardial infarction. 1870 61

Very-low-density lipoprotein (VLDL) and chylomicrons (CM) are major sources of fatty acid supply to the heart, but little is known about their metabolism in diabetic myocardium. To investigate this, working hearts isolated from control rats and diabetic rats 2 wk following streptozotocin (STZ) injection were perfused with control and diabetic lipoproteins. Analysis of the diabetic lipoproteins showed that both VLDL and CM were altered compared with control lipoproteins; both were smaller and had different apolipoprotein composition. Heparin-releasable lipoprotein lipase (HR-LPL) activity was increased in STZ-induced diabetic hearts, but tissue residual LPL activity was decreased; moreover, diabetic lipoproteins stimulated HR-LPL activity in both diabetic and control hearts. Diabetic hearts oxidized lipoprotein-triacylglycerol (TAG) to a significantly greater extent than controls (>80% compared with deposition as tissue lipid), and the oxidation rate of exogenous lipoprotein-TAG was increased significantly in diabetic hearts regardless of TAG source. Significantly increased intracardiomyocyte TAG accumulation was found in diabetic hearts, although cardiac mechanical function was not inhibited, suggesting that lipotoxicity precedes impaired cardiac performance. Glucose oxidation was significantly decreased in diabetic hearts; additionally, however, diabetic lipoproteins decreased glucose oxidation in diabetic and control hearts. These results demonstrate increased TAG-rich lipoprotein metabolism concomitant with decreased glucose oxidation in type 1 diabetic hearts, and the alterations in cardiac lipoprotein metabolism may be due to the properties of diabetic TAG-rich lipoproteins as well as the diabetic state of the myocardium. These changes were not related to cardiomyopathy at this early stage of diabetes.
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PMID:Metabolism of very-low-density lipoprotein and chylomicrons by streptozotocin-induced diabetic rat heart: effects of diabetes and lipoprotein preference. 1878 Jul 78

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.
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PMID:Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study. 1882 27

Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in the regulation of insulin resistance and adipogenesis. Cinnamon, a widely used spice in food preparation and traditional antidiabetic remedy, is found to activate PPARgamma and alpha, resulting in improved insulin resistance, reduced fasted glucose, FFA, LDL-c, and AST levels in high-caloric diet-induced obesity (DIO) and db/db mice in its water extract form. In vitro studies demonstrate that cinnamon increases the expression of peroxisome proliferator-activated receptors gamma and alpha (PPARgamma/alpha) and their target genes such as LPL, CD36, GLUT4, and ACO in 3T3-L1 adipocyte. The transactivities of both full length and ligand-binding domain (LBD) of PPARgamma and PPARalpha are activated by cinnamon as evidenced by reporter gene assays. These data suggest that cinnamon in its water extract form can act as a dual activator of PPARgamma and alpha, and may be an alternative to PPARgamma activator in managing obesity-related diabetes and hyperlipidemia.
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PMID:Improved Insulin Resistance and Lipid Metabolism by Cinnamon Extract through Activation of Peroxisome Proliferator-Activated Receptors. 1909 9

Alpha-lipoic acid (LA), a naturally occurring cofactor reported to be present in a diverse group of microorganisms, plants, and animal tissues, has been widely and successfully used as a therapy for a variety of diseases, including diabetes and heart disease. However, to date, recombinant DNA technology has not been applied for higher LA production due mainly to difficulties in the functional expression of key enzymes involved in LA production. Here, we report a study for higher LA production with the aid of chaperone plasmids, DnaKJE and trigger factor (Tf). The lipA and lplA genes encoding lipoate synthase and lipoate protein ligase in Pseudomonas fluorescens, respectively, were cloned and transformed into Escherichia coli K12. When they were overexpressed in E. coli, both LipA and LplA were expressed as inclusion bodies leading to no increase in LA production. However, when chaperone plasmids DnaKJE and Tf were coexpressed with lipA and lplA, the resulting recombinant E. coli strains showed higher LA production than the wild-type E. coli by 32-111%, respectively.
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PMID:Chaperone-aided expression of LipA and LplA followed by the increase in alpha-lipoic acid production. 1923 98

Cortisol has wide-ranging actions, namely in gluconeogenesis and glycogenesis and exerts its effects through the glucocorticoid receptor. In the present study, we examined effects of glucocorticoid receptor blockade on type 2 diabetes control using the antagonist, RU486. Obese diabetic mice received daily injections of vehicle or RU486 over 28 days. Food intake, body weight, and plasma glucose were measured frequently. At 28 days, glucose tolerance, insulin sensitivity, and plasma triglycerides were assessed. Epididymal white adipose tissue and liver were excised for measurement of gene expression. Daily administration of RU486 had no effect on body weight or food intake, but plasma glucose concentrations were significantly lowered (1.4-1.6-fold; p<0.05 to p<0.001). Glucose concentrations were also significantly reduced (2.2-fold; p<0.001) following a glucose challenge. Similarly, exogenous insulin evoked a significantly greater reduction in plasma glucose (3.6-fold; p<0.01). Gene expression analysis revealed a significant reduction in hepatic mRNA of key enzymes, namely PEPCK-C (25%; p<0.01) and G6 Pase (32%; p<0.01) and also 11beta-HSD1 (18%; p<0.05). Investigation of adipose tissue gene expression also demonstrated reduced expression in 11beta-HSD1 (47%; p<0.05) and LPL (47%; p<0.001). These data demonstrate wide-ranging effects of glucocorticoid receptor antagonism on gene expression and metabolism, illustrating the therapeutic potential of specific glucocorticoid receptor antagonists in obesity-related diabetes.
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PMID:Effect of RU486 on hepatic and adipocyte gene expression improves diabetes control in obesity-type 2 diabetes. 1967 Jan 52


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